Atherosclerosis basic mechanisms

Berliner, J. A. et al., Atherosclerosis Basic mechanisms Oxidation, inflammation and genetics, Circulation, 9, 2488,1995. 

Berliner, J.A. et al. Atherosclerosis basic mechanisms. Oxidation, inflammation, and genetics. Circulation 91 (1995) 2488-96. 

An interesting link between inflammation, atherosclerosis and NOS has been recently described [60]. In this study, the stimulation of iNOS through endothelin resulted in an increased production of NO, along with a concurrent suppression of the expression of vascular cell adhesion molecule-1 (VCAM-1). It is well known that a hallmark of inflammation is the adhesion of leukocytes to post-capillary venular endothelium and the consequent infiltration of leukocytes into the tissue interstitium. NO, by modulating cytokine-induced ECAM expression through the regulatory factor kB, may here act as antiinflammatory, keeping under control the very basic mechanisms of the atherosclerotic lesion. 

Nevertheless, the summary of the proceedings [137] of a National Heart, Lung, and Blood Institute workshop September 5-6, 1991, Bethesda, MD, entitled Antioxidants in the prevention of human atherosclerosis will serve as a conclusion "More Basic Research is needed on the mechanisms involved in the oxidative modification of LDL and on the ways in which various antioxidants influence it and More animal studies are needed to establish firmly that protection of LDL against oxidative modification does influence the progression of lesions . 

The research areas covered by the Meeting are very wide, having to do with the liver and biliary pathophysiology, nutrition, gallstone disease and atherosclerosis prevention. Scientists from the major clinical and basic disciplines provided an update overview of the complex mechanisms regulating the biosynthesis and catabolism of cholesterol and the formation and metabolism of bile acids. 

I have previously noted the minimal impact of basic lipid research on chemotherapeutic approaches to atherosclerosis. In order to close on a hopeful and somewhat more positive note, I would like to call attention to three substances which interfere with specific events in lipid biosynthesis and do so by well understood mechanisms, 3-Decynoyl-N-acetyl-cysteamine, developed in our laboratory as a substrate analogue, has been shown to block the formation of unsaturated fatty acids in certain bacteria in a highly specific manner ( 2). The compound itself is not an inhibitor but a pseudosubstrate, converted by the target enzyme into the allenic isomer,... 

In sum, basic questions remain to be clarified Is hyperglycemia an independent and additive risk factor for atherosclerotic disease What are the mechanisms - over and above chronic caloric imbalance - of the associations between hyperglycemia and hyperlipidemia, between hyperglycemia and hypertension Is a good deal of the excess atherosclerosis risk of mild maturity-onset nonketotic non-insulin-dependent diabetes in our population a result of the concomitant hypertension and/or hyperlipidemia, and not independently related to hyperglycemia per se ... 

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